The proposal involves the study of the comparative carcinogenic effects of nitroso compounds (MNU, DMNA and BHP) on pancreatic cells and explants of human, rat and hamster. The model employs dispersed acinar and ductal cells and pancreatic explants cultured in a chemically defined medium in the presence of known chemical carcinogens. The tissue preparation and culture methods have previously been reported from these laboratories. The feasibility of doing a comparative study of in vitro pancreatic carcinogenesis in human and rat has been demonstrated. The grant proposal projects an expansion of our preliminary findings to determine in a more quantitative fashion the differences (similarities) between carcinogenic steps in man, hamster and rat. In addition to morphologic information (LM and EM), it is proposed to quantitate and relate the rate of loss of acinar enzymes (amylase, lipase, chymotrypsin) with the carcinogenic process. By a combined morphologic and biochemical approach, it is hoped to identify which cell type undergoes transformation, eg. acinar duct, islet and/or stem cell. Finally by studying the relative changes in DNA, histone and nuclear nonhistone protein adducts in the presence of labeled known carcinogens, it is proposed to obtain a clearer quantitative or qualitative relationship between adduct formation and relative human, rat and hamster sensitivities to carcinogens.